Hypophosphatemia and renal phosphate wasting are observed in oncogenic osteomalacia and the humoral hypercalcemia of malignancy. Two hypercalcemic rat models, the Leydig cell tumor and the Walker breast carcinosarcoma, also demonstrate hypophosphatemia and renal phosphate wasting. Some patients and the animals bearing the Leydig cell and Walker tumors also have increased urinary cyclic AMP excretion. We have tested the Leydig-cell-tumor-culture-conditioned media for a direct effect to alter the renal handling of phosphate. We have infused culture media into the left renal artery of fed anesthetized male Sprague-Dawley rats. Control cell culture media is infused during equilibration and then for one 20-minute control clearance. The media is then switched to Leydig-cell-tumor-exposed media, is allowed to equilibrate for 10 minutes and is followed by two consecutive 20-minute experimental clearances. Time control experiments are also performed. With tumor-conditioned media, the fractional excretion of phosphate (FE(PO4)) increases from 1.2\plus or minus\0.3% in the control clearance to 4.0\plus or minus\2.2 and 3.7\plus or minus\1.1% in the first and second experimental clearances respectively (p less than 0.05 from the control clearance for both). In time control experiments, the FE(PO4) in the left kidney remains low, starting at 0.8\plus or minus\0.4% and not changing over three 20-minute clearances. In these same experiments, we are unable to detect an alteration in urinary cyclic AMP excretion. We have been able to detect a significant increase in urinary cyclic AMP excretion when bovine PTH (1-84) is infused in lactated ringers with 0.1% albumin into the left renal artery hook. Further studies are planned using the same method in volume-expanded rats whose basal FE(PO4) should be higher, and during progressive PO4 infusion after thyroparathyroidectomy.